Multi-Axis 3D Bioprinting of Cardiac Tissues with Ventricular Helical Alignment - PROJECT SUMMARY/ABSTRACT Congenital heart disease (CHD) affects over 12 million people globally and contributes to over 260,000 deaths each year. Among the most severe forms of CHD are single-ventricle heart defects, characterized by an underdeveloped or absent ventricle. Palliative repair for single-ventricle cardiac anomalies consists of a staged surgical approach culminating in the Fontan procedure, wherein the functioning ventricle is committed to supporting systemic circulation while venous return is routed passively to the lungs through a synthetic extracardiac graft without direct pump support. Although the Fontan procedure facilitates initial survival, patients experience significant long-term comorbidities due to the absence of a subpulmonary ventricular pump, ultimately leading to heart, liver, or other organ failure. One potential solution to this problem is to engineer a contractile cardiac conduit to replace the passive synthetic extracardiac graft, providing a second ventricular pump that can shift the univentricular Fontan circulation towards a more stable biventricular physiology. The Feinberg lab has recently demonstrated the use of Freeform Reversible Embedding of Suspended Hydrogels (FRESH) 3D bioprinting to produce cardiac pumps with synchronous contraction and pressure generation; however, these pumps have not achieved the contractile pressure generation necessary to serve as a substitute ventricle in the Fontan circulation. This limitation is likely due to the lack of a helical myocardial architecture, which has been shown in the adult ventricle to drive systolic ejection fraction through ventricular torsion and wall thickening. I hypothesize that cardiac conduits bioprinted with biomimetic helical architecture will demonstrate improved contractility and pressure generation similar to the native right ventricle (>15mmHg). In Aim 1, I will develop a novel multi-axis nonplanar printing platform that provides additional degrees of movement, allowing for precise deposition and alignment of material in biomimetic helical architectures. I will validate this technology by fabricating collagen conduits with varying circumferential and helical alignments and performing mechanical characterization to evaluate how fiber orientation affects biomechanical properties. In Aim 2, I will bioprint a contractile cardiac conduit with ventricular helical alignment and assess the construct for functional performance and contractility. The findings of this proposal will establish a scalable platform for engineering contractile cardiac tissues with native-like architecture and function, laying the foundation for future efforts to fabricate organ-scale cardiac constructs for organ transplantation.
